Young and healthy looking skin is a desirable attribute worldwide and the market for cosmetic products capable of improving our skin appearance is significant and growing. As we age, our natural ability to maintain young and healthy looking skin diminishes and, consequently, our skin appearance changes in response to the biological processes that take place within the skin at the cellular level. Modulation of these processes at the skin surface via intervention of specific pathways with diverse cosmetic ingredients can improve skin health and appearance. Numerous examples of how cosmetic ingredients can modulate appearance via this type of intervention are well documented.
Increased cell proliferation and migration, as well as epidermal thickness are some of the traits associated with a younger and healthy looking skin phenotype. Among the various pathways leading to such traits, inhibition of the muscarinic cholinergic system, particularly the muscarinic 3 receptor, has been shown to increase cell proliferation and migration in healthy skin. See for example, in Grando et al., “Keratinocyte muscarinic acetylcholine receptors: immunolocalization and partial characterization” Journal of Investigative Dermatology (1995), 104, 95-100; Ndoye et al. “Identification and mapping of keratinocyte muscarinic acetylcholine receptor subtypes in human epidermis” Journal of Investigative Dermatology (1998) 111, 410-416; Nguyen et al “Synergistic control of keratinocyte adhesion through muscarinic and nicotinic acetylcholine receptor subtypes” Exp. Cell. Res. (2004) 294, 534-549; Kurzen et al. “The non-neuronal cholinergic system of human skin” Horm. Metab. Res. (2007) 39, 125-137.
Muscarinic receptor antagonists have been claimed in medications used to treat skin diseases. For example, WO0110427 describes the use of anti-muscarinic agents to treat skin disorders including psoriasis, atopic dermatitis, eczema, urticaria, acne, etc. WO09068876 describes the use of muscarinic receptor antagonists with antibacterial and sebum suppressive activities in the manufacture of medicaments to treat bacterial skin infections. Further, WO09150408 and WO09068876 describe the use of muscarinic receptor antagonists in compositions to treat acne and seborrhea, for example.
Various compositions comprising some N-aralkylcarbonyldiamines or related structures have been described, for example in U.S. Pat. No. 5,192,779 (Fujisawa Pharmaceutical Co.) and Smith et al., “Physiologically active compounds. III. Hydrochlorides of amino esters of phenylcuclohexylglycolic acids, of amides of benzilic, phenylcyclohexyl- and dicyclohexylglycolic, and phenylcyclohexylacetic acids; 2-methylthioethyl ester methiodides of substituted benzilic acids”, Journal of Organic Chemistry (1959) 1301-1309. However the specific derivatives used are different from the compounds of our invention. Moreover, none of these compositions are recognized for use as cosmetics for personal care benefits.
It is also noted that compounds of the invention differ from many somewhat related compounds in that compounds comprising primary amines, secondary amines and secondary amides (defined as compounds containing a —CONH— functional group) are not included in the scope of our compounds.
The novel N-aralkylcarbonyldiamine compounds of the invention have several advantages for personal care compositions compared to N-aralkylcarbonyldiamines and muscarinic receptor antagonists described in the prior art. For example, compounds of the invention are not quaternized, which distinguishes them from some of the currently used muscarinic receptor antagonists, for example oxyphenonium bromide, glycopyrrolate, ipatropium, tiotropium to name a few. By “not quaternized” is meant that they do not have an additional bond attaching an alkyl group to the nitrogen atom of the tertiary amine which provides a permanent positive charge. Quaternized compounds are less desirable because they do not penetrate skin as effectively compared to when they are in an unquaternized form. The novel unquaternized N-aralkylcarbonyldiamines are therefore better suited for skin applications. Further, the inventive compounds do not contain ester functional groups, unlike many of the currently used muscarinic receptor antagonists such as oxybutynin, oxyphenonium bromide, hyoscyamine, dicyclomine, propiverine to name a few. Compounds with ester groups are less desirable for skin compositions since they are prone to hydrolysis once formulated, especially under high heat storage conditions. The compounds of the invention contain tertiary amide bonds which are known to be more stable than their corresponding esters.